skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: Development of human hippocampal subfield microstructure and relation to associative inference
Abstract The hippocampus is a complex brain structure composed of subfields that each have distinct cellular organizations. While the volume of hippocampal subfields displays age-related changes that have been associated with inference and memory functions, the degree to which the cellular organization within each subfield is related to these functions throughout development is not well understood. We employed an explicit model testing approach to characterize the development of tissue microstructure and its relationship to performance on 2 inference tasks, one that required memory (memory-based inference) and one that required only perceptually available information (perception-based inference). We found that each subfield had a unique relationship with age in terms of its cellular organization. While the subiculum (SUB) displayed a linear relationship with age, the dentate gyrus (DG), cornu ammonis field 1 (CA1), and cornu ammonis subfields 2 and 3 (combined; CA2/3) displayed nonlinear trajectories that interacted with sex in CA2/3. We found that the DG was related to memory-based inference performance and that the SUB was related to perception-based inference; neither relationship interacted with age. Results are consistent with the idea that cellular organization within hippocampal subfields might undergo distinct developmental trajectories that support inference and memory performance throughout development.  more » « less
Award ID(s):
2148700
PAR ID:
10486088
Author(s) / Creator(s):
; ; ;
Publisher / Repository:
Cerebral Cortex
Date Published:
Journal Name:
Cerebral Cortex
Volume:
33
Issue:
18
ISSN:
1047-3211
Page Range / eLocation ID:
10207 to 10220
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract Previous research has established important developmental changes in sleep and memory during early childhood. These changes have been linked separately to brain development, yet few studies have explored their interrelations during this developmental period. The goal of this report was to explore these associations in 200 (100 female) typically developing 4- to 8-year-old children. We examined whether habitual sleep patterns (24-h sleep duration, nap status) were related to children’s performance on a source memory task and hippocampal subfield volumes. Results revealed that, across all participants, after controlling for age, habitual sleep duration was positively related to source memory performance. In addition, in younger (4–6 years, n = 67), but not older (6–8 years, n = 70) children, habitual sleep duration was related to hippocampal head subfield volume (CA2-4/DG). Moreover, within younger children, volume of hippocampal subfields varied as a function of nap status; children who were still napping (n = 28) had larger CA1 volumes in the body compared to children who had transitioned out of napping (n = 39). Together, these findings are consistent with the hypothesis that habitually napping children may have more immature cognitive networks, as indexed by hippocampal integrity. Furthermore, these results shed additional light on why sleep is important during early childhood, a period of substantial brain development. 
    more » « less
  2. The hippocampus consists of a stereotyped neuronal circuit repeated along the septal-temporal axis. This transverse circuit contains distinct subfields with stereotyped connectivity that support crucial cognitive processes, including episodic and spatial memory. However, comprehensive measurements across the transverse hippocampal circuit in vivo are intractable with existing techniques. Here, we developed an approach for two-photon imaging of the transverse hippocampal plane in awake mice via implanted glass microperiscopes, allowing optical access to the major hippocampal subfields and to the dendritic arbor of pyramidal neurons. Using this approach, we tracked dendritic morphological dynamics on CA1 apical dendrites and characterized spine turnover. We then used calcium imaging to quantify the prevalence of place and speed cells across subfields. Finally, we measured the anatomical distribution of spatial information, finding a non-uniform distribution of spatial selectivity along the DG-to-CA1 axis. This approach extends the existing toolbox for structural and functional measurements of hippocampal circuitry. 
    more » « less
  3. Abstract Efficient memory-based problem-solving strategies are a cardinal feature of expertise across a wide range of cognitive domains in childhood. However, little is known about the neurocognitive mechanisms that underlie the acquisition of efficient memory-based problem-solving strategies. Here we develop, to the best of our knowledge, a novel neurocognitive process model of latent memory processes to investigate how cognitive training designed to improve children’s problem-solving skills alters brain network organization and leads to increased use and efficiency of memory retrieval-based strategies. We found that training increased both the use and efficiency of memory retrieval. Functional brain network analysis revealed training-induced changes in modular network organization, characterized by increase in network modules and reorganization of hippocampal-cortical circuits. Critically, training-related changes in modular network organization predicted performance gains, with emergent hippocampal, rather than parietal cortex, circuitry driving gains in efficiency of memory retrieval. Our findings elucidate a neurocognitive process model of brain network mechanisms that drive learning and gains in children’s efficient problem-solving strategies. 
    more » « less
  4. Despite the early development of causal reasoning (CR), and its potential for shaping scientific literacy, we have little understanding of its structural origins. Specifically, is CR a unique capability that develops relatively independently or is it largely dependent on broader, more fundamental, cognitive abilities? Executive Functioning (EF) is an especially promising contributor to CR based on its already established role in related skills like planning and problem solving (e.g., Diamond, 2013). To begin exploring this potential relationship, we assessed 123 three (Mage = 3.42 years) and 64 five year olds’ (Mage = 5.36 years) performance on two CR tasks (counterfactual reasoning and causal inference), each of which we expected might be influenced in different ways by distinct EF skills. The counterfactual reasoning task (Guajardo & Turley-Ames, 2004) required children to generate alternative courses of action that would lead to different outcomes in fictional vignettes. The causal inference task (Das Gupta & Bryant, 1989) required children to compare pictures taken before and after a transformation (e.g., broken flowerpot and intact flowerpot) and to select a tool (e.g., glue) that could have caused it. We measured EF with three tasks: flanker (inhibition), count and label (working memory), and dimensional change card sort (cognitive flexibility). Finally, we measured children’s vocabulary and processing speed. To explore the relationship between EF and CR, we conducted a series of four linear regressions predicting causal inference and counterfactual reasoning ability in 3 and 5 year olds. Of all our measures, only vocabulary and inhibitory control emerged as significant predictors of causal inference ability for both 3 (βvocab = .04, p = .002, and βinhib = .04, p = .04) and 5 year olds (βvocab = .03, p = .01, and βinhib = .02, p = .04). Similarly, inhibitory control emerged as the only significant predictor of counterfactual reasoning in 3 year olds, βinhib = .03, p = .03. In contrast, for 5 year olds, working memory was the only significantly predictor of counterfactual reasoning, βWM = .71, p = .02. These results suggest that causal inference skills are stably supported by inhibitory control throughout early childhood. The story for counterfactual reasoning, however, appears to be somewhat more complex. Consistent with previous work (Beck, Riggs & Gorniak, 2009), inhibitory control supported counterfactual reasoning ability in our 3-year-old sample. However, inhibitory control did not significantly predict counterfactual reasoning in 5 year olds, it was supported by working memory instead. One explanation for this difference might have to do with the sophistication of children’s counterfactual reasoning skills at these different ages. Taken together, these results suggest that CR does not develop as a unique capacity, but instead likely relies on EFs that influence different CR skills in distinct ways across development. This represents an initial step in understanding early CR skills, which are promising contributors to emerging scientific literacy. 
    more » « less
  5. IntroductionThe effectiveness of neural interfacing devices depends on the anatomical and physiological properties of the target region. Multielectrode arrays, used for neural recording and stimulation, are influenced by electrode placement and stimulation parameters, which critically impact tissue response. This study presents a multiscale computational model that predicts responses of neurons in the hippocampus—a key brain structure primarily involved in memory formation, especially the conversion of short-term memories into long-term storage—to extracellular electrical stimulation, providing insights into the effects of electrode positioning and stimulation strategies on neuronal response. MethodsWe modeled the rat hippocampus with highly detailed axonal projections, integrating the Admittance Method to model propagation of the electric field in the tissue with the NEURON simulation platform. The resulting model simulates electric fields generated by virtual electrodes in the perforant path of entorhinal cortical (EC) axons projecting to the dentate gyrus (DG) and predicts DG granule cell activation via synaptic inputs. ResultsWe determined stimulation amplitude thresholds required for granule cell activation at different electrode placements along the perforant path. Membrane potential changes during synaptic activation were validated against experimental recordings. Additionally, we assessed the effects of bipolar electrode placements and stimulation amplitudes on direct and indirect activation. ConclusionStimulation amplitudes above 750 μA consistently activate DG granule cells. Lower stimulation amplitudes are required for axonal activation and downstream synaptic transmission when electrodes are placed in the molecular layer, infra-pyramidal region, and DG crest. SignificanceThe study and underlying methodology provide useful insights to guide the stimulation protocol required to activate DG granule cells following the stimulation of EC axons; the complete realistic 3D model presented constitutes an invaluable tool to strengthen our understanding of hippocampal response to electrical stimulation and guide the development and placement of prospective stimulation devices and strategies. 
    more » « less